ID HPPD_MOUSE Reviewed; 393 AA.
AC P49429; P97322; Q3UEQ0; Q91WV9;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 24-JAN-2024, entry version 176.
DE RecName: Full=4-hydroxyphenylpyruvate dioxygenase;
DE EC=1.13.11.27 {ECO:0000250|UniProtKB:P32755};
DE AltName: Full=4-hydroxyphenylpyruvic acid oxidase;
DE Short=4HPPD;
DE Short=HPD;
DE Short=HPPDase;
DE AltName: Full=F Alloantigen;
DE Short=F protein;
GN Name=Hpd;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=7774914; DOI=10.1016/0888-7543(95)80122-3;
RA Endo F., Awata H., Katoh H., Matsuda I.;
RT "A nonsense mutation in the 4-hydroxyphenylpyruvic acid dioxygenase gene
RT (Hpd) causes skipping of the constitutive exon and hypertyrosinemia in
RT mouse strain III.";
RL Genomics 25:164-169(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-379, AND VARIANT ASN-104.
RC STRAIN=CBA/J; TISSUE=Liver;
RX PubMed=1709870; DOI=10.1002/eji.1830210521;
RA Schofield J.P., Vijayakumar R.K., Oliveira D.B.G.;
RT "Sequences of the mouse F protein alleles and identification of a T cell
RT epitope.";
RL Eur. J. Immunol. 21:1235-1240(1991).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-211; SER-226 AND SER-250, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-211 AND SER-250, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-132, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Catalyzes the conversion of 4-hydroxyphenylpyruvic acid to
CC homogentisic acid, one of the steps in tyrosine catabolism.
CC {ECO:0000250|UniProtKB:P32755}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-(4-hydroxyphenyl)pyruvate + O2 = CO2 + homogentisate;
CC Xref=Rhea:RHEA:16189, ChEBI:CHEBI:15379, ChEBI:CHEBI:16169,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:36242; EC=1.13.11.27;
CC Evidence={ECO:0000250|UniProtKB:P32755};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16190;
CC Evidence={ECO:0000250|UniProtKB:P32755};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:P32755};
CC Note=Binds 1 Fe cation per subunit. {ECO:0000250|UniProtKB:P32755};
CC -!- PATHWAY: Amino-acid degradation; L-phenylalanine degradation;
CC acetoacetate and fumarate from L-phenylalanine: step 3/6.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P32755}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P32755}.
CC Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P32755};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P32755}. Golgi
CC apparatus membrane {ECO:0000250|UniProtKB:P32755}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:P32755}.
CC -!- POLYMORPHISM: There are two alleles (F1 and F2), F2 has Asp-104 and F1
CC has Asn-104. Mice are completely tolerant to the self form of the
CC protein, but make a good antibody response to immunization with the
CC non-self form.
CC -!- DISEASE: Note=Defects in Hpd are the cause of tyrosinemia type III.
CC -!- SIMILARITY: Belongs to the 4HPPD family. {ECO:0000305}.
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DR EMBL; D29987; BAA06267.1; -; mRNA.
DR EMBL; AK149416; BAE28861.1; -; mRNA.
DR EMBL; BC013343; AAH13343.1; -; mRNA.
DR EMBL; X59530; CAA42111.1; -; mRNA.
DR CCDS; CCDS39265.1; -.
DR PIR; A60236; A60236.
DR RefSeq; NP_032303.1; NM_008277.2.
DR AlphaFoldDB; P49429; -.
DR SMR; P49429; -.
DR BioGRID; 200405; 3.
DR STRING; 10090.ENSMUSP00000031398; -.
DR iPTMnet; P49429; -.
DR PhosphoSitePlus; P49429; -.
DR SwissPalm; P49429; -.
DR jPOST; P49429; -.
DR MaxQB; P49429; -.
DR PaxDb; 10090-ENSMUSP00000031398; -.
DR PeptideAtlas; P49429; -.
DR ProteomicsDB; 273167; -.
DR Antibodypedia; 31595; 360 antibodies from 31 providers.
DR DNASU; 15445; -.
DR Ensembl; ENSMUST00000031398.14; ENSMUSP00000031398.8; ENSMUSG00000029445.14.
DR GeneID; 15445; -.
DR KEGG; mmu:15445; -.
DR UCSC; uc008znj.1; mouse.
DR AGR; MGI:96213; -.
DR CTD; 3242; -.
DR MGI; MGI:96213; Hpd.
DR VEuPathDB; HostDB:ENSMUSG00000029445; -.
DR eggNOG; KOG0638; Eukaryota.
DR GeneTree; ENSGT00530000063474; -.
DR HOGENOM; CLU_034004_3_1_1; -.
DR InParanoid; P49429; -.
DR OMA; DPFPVKG; -.
DR OrthoDB; 34818at2759; -.
DR PhylomeDB; P49429; -.
DR TreeFam; TF300622; -.
DR Reactome; R-MMU-8963684; Tyrosine catabolism.
DR SABIO-RK; P49429; -.
DR UniPathway; UPA00139; UER00362.
DR BioGRID-ORCS; 15445; 2 hits in 78 CRISPR screens.
DR ChiTaRS; Hpd; mouse.
DR PRO; PR:P49429; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; P49429; Protein.
DR Bgee; ENSMUSG00000029445; Expressed in left lobe of liver and 75 other cell types or tissues.
DR ExpressionAtlas; P49429; baseline and differential.
DR Genevisible; P49429; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; ISO:MGI.
DR GO; GO:0003868; F:4-hydroxyphenylpyruvate dioxygenase activity; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0006559; P:L-phenylalanine catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006572; P:tyrosine catabolic process; ISS:UniProtKB.
DR CDD; cd07250; HPPD_C_like; 1.
DR CDD; cd08342; HPPD_N_like; 1.
DR Gene3D; 3.10.180.10; 2,3-Dihydroxybiphenyl 1,2-Dioxygenase, domain 1; 2.
DR InterPro; IPR005956; 4OHPhenylPyrv_dOase.
DR InterPro; IPR041735; 4OHPhenylPyrv_dOase_C.
DR InterPro; IPR041736; 4OHPhenylPyrv_dOase_N.
DR InterPro; IPR029068; Glyas_Bleomycin-R_OHBP_Dase.
DR InterPro; IPR004360; Glyas_Fos-R_dOase_dom.
DR InterPro; IPR037523; VOC.
DR NCBIfam; TIGR01263; 4HPPD; 1.
DR PANTHER; PTHR11959; 4-HYDROXYPHENYLPYRUVATE DIOXYGENASE; 1.
DR PANTHER; PTHR11959:SF12; 4-HYDROXYPHENYLPYRUVATE DIOXYGENASE; 1.
DR Pfam; PF00903; Glyoxalase; 2.
DR PIRSF; PIRSF009283; HPP_dOase; 1.
DR SUPFAM; SSF54593; Glyoxalase/Bleomycin resistance protein/Dihydroxybiphenyl dioxygenase; 1.
DR PROSITE; PS51819; VOC; 2.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Dioxygenase; Endoplasmic reticulum;
KW Golgi apparatus; Iron; Membrane; Metal-binding; Oxidoreductase;
KW Phenylalanine catabolism; Phosphoprotein; Reference proteome; Repeat;
KW Tyrosine catabolism.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P32754"
FT CHAIN 2..393
FT /note="4-hydroxyphenylpyruvate dioxygenase"
FT /id="PRO_0000088389"
FT DOMAIN 18..149
FT /note="VOC 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT DOMAIN 180..338
FT /note="VOC 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT BINDING 183
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P32755"
FT BINDING 266
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P32755"
FT BINDING 349
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P32755"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0000250|UniProtKB:P32754"
FT MOD_RES 132
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 211
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT MOD_RES 250
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT VARIANT 104
FT /note="D -> N (in allele F1)"
FT /evidence="ECO:0000269|PubMed:1709870"
FT CONFLICT 2..6
FT /note="TTYNN -> VDYWD (in Ref. 4; CAA42111)"
FT /evidence="ECO:0000305"
FT CONFLICT 64
FT /note="Q -> R (in Ref. 1; BAA06267)"
FT /evidence="ECO:0000305"
FT CONFLICT 120..121
FT /note="EP -> DA (in Ref. 4; CAA42111)"
FT /evidence="ECO:0000305"
FT CONFLICT 206
FT /note="F -> S (in Ref. 2; BAE28861)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 393 AA; 45054 MW; 70B42A4E4744744A CRC64;
MTTYNNKGPK PERGRFLHFH SVTFWVGNAK QAASFYCNKM GFEPLAYRGL ETGSREVVSH
VIKQGKIVFV LCSALNPWNK EMGDHLVKHG DGVKDIAFEV EDCDHIVQKA RERGAKIVRE
PWVEQDKFGK VKFAVLQTYG DTTHTLVEKI NYTGRFLPGF EAPTYKDTLL PKLPRCNLEI
IDHIVGNQPD QEMQSASEWY LKNLQFHRFW SVDDTQVHTE YSSLRSIVVT NYEESIKMPI
NEPAPGRKKS QIQEYVDYNG GAGVQHIALK TEDIITAIRH LRERGTEFLA APSSYYKLLR
ENLKSAKIQV KESMDVLEEL HILVDYDEKG YLLQIFTKPM QDRPTLFLEV IQRHNHQGFG
AGNFNSLFKA FEEEQALRGN LTDLEPNGVR SGM
//
